Estimation of amyloid distribution by [ 18 F]flutemetamol PET predicts the neuropathological phase of amyloid β-protein deposition

Abstract

The deposition of the amyloid β-protein (Aβ) in senile plaques is one of the histopathological hallmarks of Alzheimer's disease (AD). Aβ-plaques arise first in neocortical areas and, then, expand into further brain regions in a process described by 5 phases. Since it is possible to identify amyloid pathology with radioactive-labeled tracers by positron emission tomography (PET) the question arises whether it is possible to distinguish the neuropathological Aβ-phases with amyloid PET imaging. To address this question we reassessed 97 cases of the end-of-life study cohort of the phase 3 [¹⁸F]flutemetamol trial (ClinicalTrials.gov identifiers NCT01165554, and NCT02090855) by combining the standardized uptake value ratios (SUVRs) with pons as reference region for cortical and caudate nucleus-related [¹⁸F]flutemetamol-retention. We tested them for their prediction of the neuropathological pattern found at autopsy. By defining threshold levels for cortical and caudate nucleus SUVRs we could distinguish different levels of [¹⁸F]flutemetamol uptake termed PET-Aβ phase estimates. When comparing these PET-Aβ phase estimates with the neuropathological Aβ-phases we found that PET-Aβ phase estimate 0 corresponded with Aβ-phases 0-2, 1 with Aβ-phase 3, 2 with Aβ-phase 4, and 3 with Aβ-phase 5. Classification using the PET-Aβ phase estimates predicted the correct Aβ-phase in 72.16% of the cases studied here. Bootstrap analysis was used to confirm the robustness of the estimates around this association. When allowing a range of ± 1 phase for a given Aβ-phase correct classification was given in 96.91% of the cases. In doing so, we provide a novel method to convert SUVR-levels into PET-Aβ phase estimates that can be easily translated into neuropathological phases of Aβ-deposition. This method allows direct conclusions about the pathological distribution of amyloid plaques (Aβ-phases) in vivo. Accordingly, this method may be ideally suited to detect early preclinical AD-patients, to follow them with disease progression, and to provide a more precise prognosis for them based on the knowledge about the underlying pathological phase of the disease.

https://ift.tt/2Bp4Hzn

Monitoring of patients with metastatic melanoma treated with immune checkpoint inhibitors using PET–CT

Abstract

Immune checkpoint inhibitors (ICI) have revolutionized therapy of metastatic melanoma. The first ICI was ipilimumab, a cytotoxic T lymphocyte-associated Ag 4 (CLTA-4) inhibitor with response rates of approximately 11% and disease control of 22%. The programmed cell death 1 (PD-1) inhibitors, such as pembrolizumab and nivolumab, led to longer progression-free survival and overall survival rates with fewer side effects. Molecular imaging techniques, such as positron emission tomography–computed tomography (PET–CT) with 2-deoxy-2-(¹⁸F)fluoro-d-glucose (¹⁸F-FDG) are in use for staging and therapy monitoring of metastatic melanoma. However, classical radiological imaging criteria such as RECIST and WHO are not appropriate for the assessment of ICI response. New immune-related criteria have been defined such as iRECIST or irRC, which refer to radiological imaging modalities. Until now only a few studies report on immunotherapy response assessment based on ¹⁸F-FDG PET–CT. The classical criteria used for therapy monitoring with ¹⁸F-FDG PET, such as the EORTC criteria, are not suitable for ICI monitoring. In this focussed review, we present different criteria proposed for ICI monitoring with ¹⁸F-FDG and their limitations. One goal is to early identify non-responders to tailor immunotherapy. Another question is pseudoprogression and how to interpret the ¹⁸F-FDG images for response assessment. Finally, the definition of ¹⁸F-FDG criteria which can be used to identify progress is crucial and discussed in the review. The recent presented PET-based immune-related criteria, the so-called PERCIMT (PET Response Evaluation Criteria for IMmunoTherapy) are presented. Furthermore, new tracers are discussed.

https://ift.tt/2L507Ga

Monitoring of patients with metastatic melanoma treated with immune checkpoint inhibitors using PET–CT

Abstract

Immune checkpoint inhibitors (ICI) have revolutionized therapy of metastatic melanoma. The first ICI was ipilimumab, a cytotoxic T lymphocyte-associated Ag 4 (CLTA-4) inhibitor with response rates of approximately 11% and disease control of 22%. The programmed cell death 1 (PD-1) inhibitors, such as pembrolizumab and nivolumab, led to longer progression-free survival and overall survival rates with fewer side effects. Molecular imaging techniques, such as positron emission tomography–computed tomography (PET–CT) with 2-deoxy-2-(¹⁸F)fluoro-d-glucose (¹⁸F-FDG) are in use for staging and therapy monitoring of metastatic melanoma. However, classical radiological imaging criteria such as RECIST and WHO are not appropriate for the assessment of ICI response. New immune-related criteria have been defined such as iRECIST or irRC, which refer to radiological imaging modalities. Until now only a few studies report on immunotherapy response assessment based on ¹⁸F-FDG PET–CT. The classical criteria used for therapy monitoring with ¹⁸F-FDG PET, such as the EORTC criteria, are not suitable for ICI monitoring. In this focussed review, we present different criteria proposed for ICI monitoring with ¹⁸F-FDG and their limitations. One goal is to early identify non-responders to tailor immunotherapy. Another question is pseudoprogression and how to interpret the ¹⁸F-FDG images for response assessment. Finally, the definition of ¹⁸F-FDG criteria which can be used to identify progress is crucial and discussed in the review. The recent presented PET-based immune-related criteria, the so-called PERCIMT (PET Response Evaluation Criteria for IMmunoTherapy) are presented. Furthermore, new tracers are discussed.

https://ift.tt/2L507Ga

Tribulus terrestris improves metronidazole-induced impaired fertility in the male mice

Introduction: Fruit extract of Tribulus terrestris (TT) bears aphrodisiac and antioxidative properties. Antimicrobial drug, metronidazole (MTZ) impairs the spermatogenic activity and fertility in males.
Objective: Validation of the use of fruit extract of TT as a supplement against MTZ-induced fertility impairment in males.

Methods: Adult Swiss strain male mice were administered with 500mg/kgBW/day of MTZ for 28 days. Low (100mg/kgBW/day) and high (200mg/kgBW/day) doses of TT were administered simultaneously with MTZ (500mg/kgBW/day) for same duration. All males were cohabited with virgin proestrus females. Vaginal plug formation was observed to calculate the libido index. Cohabited females were sacrificed on fifteenth day of gestation to dissect out the ovaries and uteri. Fertility index, quantal pregnancy, pre-implantation and post-implantation losses were calculated. 

Results: MTZ-treated males showed unaltered mating ability, however, the females impregnated by such males exhibited marked alterations in the fertility index, quantal pregnancy and pre- and post-implantation losses. Supplementation with low dose of TT failed to restore such reproductive toxicities exhibited by administration of MTZ. However, the altered reproductive toxicities were reinstated to control values following supplementation with high dose of TT.
Conclusion: The fruit extract of TT may emerge as an effective herbal remedy, correcting the drug-induced fertility impairments in males.

Keywords: Female mice, fertility, male mice, metronidazole, Tribulus terrestris.

 

 

https://ift.tt/2Pl2eJ6

Cystic fibrosis in Tunisian children: a review of 32 children

Background: Cystic fibrosis is rare in Tunisia.Its diagnosis requires experienced specialists. Its prognosis is poor in developing countries.
Objectives: To study the epidemiologic, clinical, genetic features and the therapeutic challenges of cystic fibrosis in Tunisian children.
Methods: Covering a period of 21 years, this retrospective study included all patients with a definite diagnosis of cystic fibrosis from the Pediatrics Department B of The Children's Hospital of Tunis.
Results: Data from 32 children (14 boys and 18 girls) were collected. The diagnosis was made during the first year of life in 28 cases. Meconium ileus was found in 5 cases, respiratory manifestations in 22 cases, chronic diarrhea in 19 cases, faltering growth in 17 cases and a pseudo Barter syndrome in 2 cases. The sweat chloride test was positive in all cases. The most frequent mutation was F508del (56% of cases). Respiratory complications marked the outcome. Among our 32 patients, 15 patients (50%) died at an average age of 5 years and 3 months, mainly due to respiratory failure. The mean age of the surviving patients was 5 years.
Conclusion: Cystic fibrosis prognosis is poor in our series compared to developed countries due to the longer diagnostic delay and the limited therapeutic options.

Keywords: Cystic fibrosis, children, Tunisia.

https://ift.tt/2PlxwQ7

A study on visual, audio and tactile reaction time among medical students at Kampala International University in Uganda

Background: Reaction time (RT) is an indicator of neural activity, however, its variation due to visual (VRT), audio (ART) and tactile (TRT) in African medical students has not been investigated. The aim of the study was to determine relationships between VRT, ART and TRT amongst medical students in Uganda.
Materials and methods: This was a cross sectional study, the body mass index (BMI) and RT (i.e. VRT, ART and TRT) were determined using weighing scale with standiometer and the catch a ruler experiment respectively. A questionnaire was administered to collect information on participant's lifestyle patterns and analysis was done using SPSS Version 20.
Results: The mean (± SEM) VRT, ART and TRT in the study were found to be 0.148 ± 0.002s, 0.141 ± 0.002s and 0.139 ± 0.003s respectively. A strong correlation between TRT and ART was found to exist in the youthful Ugandan medical student's population. Furthermore, significant differences in ART and VRT were observed with sex, although these were absent amongst preclinical and clinical students, showing the importance of sex in RT.
Conclusion: The low VRT and ART in Ugandan medical students is indicative of a healthy somatosensory connectivity, thus of academic importance.

Keywords: Reaction time, cognitive performance, neural health, medical education.

https://ift.tt/2MYU1c3

A randomized control trial comparing train of four ratio > 0.9 to clinical assessment of return of neuromuscular function before endotracheal extubation on critical respiratory events in adult patients undergoing elective surgery at a tertiary hospital in

Background: There is increasing evidence that the incidence of postoperative residual paresis after using neuromuscular blockers ranges from 24 to 50% in post anaesthesia care unit (PACU) and is associated with postoperative complications such as critical respiratory events as evidenced by hypoxia, hypoventilation and upper airway obstruction. Quantitative neuromuscular monitoring (such as the assessment of Train of four (TOF) ratio) and reversal of neuromuscular blockers has been shown to reduce postoperative residual paresis. There are very few outcome studies on effect of residual paresis in PACU. There is a paucity of published randomized controlled trials investigating whether using a TOF ratio ≥0.9 before endotracheal extubation compared to clinical assessment of return of neuromuscular function reduces the incidence of critical respiratory events in PACU.
Objective: To determine whether using TOF ratio ≥ 0.9 compared to clinical assessment of return of neuromuscular function before endotracheal extubation reduces the incidence of critical respiratory events in PACU
Methods: Onehundred sixty eight adult patients in ASA physical status I and II requiring general anaesthesia for elective surgery with cisatracurium as the muscle relaxant were randomized into 2 groups of 84 each. Group 1 were patients who required a TOF ratio of ≥0.9 before extubation. Group 2 patients were extubated based on clinical assessment of return of adequate neuromuscular function by the anaesthetist as is the standard of practice at the Aga Khan University hospital Nairobi. General anaesthesia was standardized in both groups. Both the investigators and patients were blinded during the study. Once the patient was transferred to PACU, oxygen saturation (SP02), respiratory rate and any signs of upper airway obstruction as demonstrated by stridor, laryngospasms or requirement of any airway manipulation was recorded for the first 30 minutes. Duration of anaesthesia and surgery was also recorded. Patient demographics were recorded and analyzed.
Results: There was no statistical difference between the 2 groups in terms of patient demographics, duration of surgery and anaesthesia and duration since last muscle relaxant was given. In terms of hypoxia on arrival in PACU, the incidence of mild hypoxia (SPO2 90-93%) was 11% in clinical assessment groupversus 5% in TOF group P-value 0.149 while severe hypoxia (SPO2 <90%) was 19% versus 10% P-value 0.078. During the first 30 minutes in PACU, the incidence of mild hypoxia (SPO2 90-93%) was statistically significant between the 2 groups (12% in clinical assessment group versus 1% in TOF group, P-value 0.005) while severe hypoxia (SPO2 <90%) was 7% versus 5%, P-value 0.373. The incidence of upper airway obstruction was statistically significant between the two groups (45% in clinical assessment group versus 14% in TOF group P-value<0.0001 for patients requiring airway maneuver, 21% versus 2% P-value <0.0001 for those who required tactile stimulation and 31% versus 12% were snoring, P-value 0.003. Logistic regression analysis revealed TOF group was less likely associated with mild hypoxia (OR 0.09 95% CI 0.01-0.71 P-value 0.023), tactile stimulation (OR 0.09 95% CI 0.02-0.40 P-value 0.002), airway maneuver (OR 0.20 95% CI 0.10-0.43 P-value <0.001) and snoring (OR 0.30 95% CI 0.13-0.68 P-value 0.04).
Conclusion: Among this population, there is a lower incidence of critical respiratory events in PACU with the use of neuromuscular monitoring using TOF ratio ≥0.9 to assess neuromuscular function before endotracheal extubation compared with the use of clinical assessment methods.

Keywords: Randomized control trial, neuromuscular function, elective surgery, Nairobi.

https://ift.tt/2BmGUzY

MR imaging of intracranial solitary fibrous tumor: a retrospective study of 7 cases

Objective: To investigate the MR imaging diagnostic features of intracranial solitary fibrous tumors (ISFTs).
Materials and methods: Seven patients (mean age of 52.9 years; M:F=3:4) with histopathologically proven ISFTs were identified at our institute. Clinical presentations and pathological features were reviewed. MR Imaging findings including signal intensity, gadopentetate dimeglumine enhanced pattern, and diffusion-weighted imaging (DWI) characterization of the tumors were retrospectively evaluated.
Results: Six tumors showed a multi-lobular contour. Five tumors showed heterogeneous signal intensity, and two tumors showed homogeneous signal intensity on T1WI. Low signal intensity linear, curved or interlacing lines were observed within the tumors in all seven cases. Seven tumors demonstrated moderate or strong enhancement, six showed heterogeneous enhancement, and one homogenous enhancement. All tumors showed heterogeneous signal intensity on DWI.A ring–like high signal intensity band distributed around within the tumor was noted in six cases on DWI.
Conclusion: Diagnostic evidence for ISFT on MR image includes heterogeneous signal intensity, intense enhancement of T2 signal intensity, low signal intensity lines within the tumor, heterogeneous signal intensity on DWI and a ring-like band around the tumor on DWI.

Keywords: Intracranial Solitary Fibrous Tumor, Magnetic resonance imaging, Diffusion-weighted Imaging.

https://ift.tt/2MCzAEM

AGREE-II Appraisal of a clinical algorithm for hypotonia assessment

Objective: The objective of this study was to systematically appraise the quality of an evidenced-based clinical algorithm for the clinical assessment of hypotonia in children.
Design: The Appraisal of Guidelines for Research and Evaluation (AGREE) II tool with 23 items and six domains was used. The study was located in South Africa. Ten appraisers, who were recruited based on specific selection criteria, completed the assessment.
Results: Nine appraisers recommended the EBCA without any modification. Scope and purpose (94%), stakeholder involvement (91%) and editorial independence (99%) were rated the highest with the lower scoring domains being clarity of presentation (85%) and applicability (86%) due to clarity required in areas of resource implications and auditing and monitoring criteria. Inter-rater reliability was strong (ICC 0.7) amongst the appraisers in this study.
Conclusion: This is the first independent assessment of the methodological rigour and transparency of a clinical algorithm using the AGREE-II instrument. Determining the quality of the EBCA for practice is essential as this would ultimately aid clinicians towards more accurate clinical assessment of hypotonia which would inevitably impact outcomes and management of the child presenting with this symptom. Whilst the AGREE-II provided initial feedback on the methodological rigour of development, understanding that the AGREE-II instrument evaluates the guideline development process and not the content is also essential in order to consider the next stage which would be to consider clinicians feedback on the clinical utility of this EBCA.

Keywords: AGREE-II; clinical algorithm; hypotonia, low muscle tone; paediatrics.

https://ift.tt/2BmGPfE

Neuroleptic malignant syndrome in a young adult female at the university of Benin Teaching Hospital: a case report

Background: Neuroleptic malignant syndrome is a rare but life-threatening idiosyncratic complication following the use of antipsychotic agents, anaesthesia and surgery. It is characterized by hyperthermia, muscle rigidity, autonomic disturbances and mental state alterations.
Case: A 31 year old female weighing 60kg received a depot preparation of Fluphenazine on account of depression with psychotic features observed two days prior to elective Cholecystectomy under general anaesthesia. Surgery and anaesthesia were essentially uneventful. Forty eight hours post-operatively, the patient developed features suggestive of neuroleptic malignant syndrome complicated by aspiration pneumonitis. This necessitated her admission into the intensive care unit. She had prolonged stay in the intensive care unit, where she was mechanically ventilated, developed deep venous thrombosis of the left upper limb and required tracheostomy on account of prolonged endotracheal intubation. Patient recovered fully following bromocriptine and dantrolene therapy. She was discharged home after 60 days on admission and has remained in good health.
Conclusion: Though rare, neuroleptic malignant syndrome can occur in young adult females following use of antipsychotics, anaesthesia and surgery. Its clinical course can be prolonged and distressing with the use of depot preparations. Early diagnosis and prompt supportive measures are essential to reduce morbidity and mortality.

Keywords: Neuroleptic malignant syndrome, adult female, University of Benin Teaching Hospital.

https://ift.tt/2Pmerxp

Substance abuse among students in selected secondary schools of an urban community of Oyo-state, South West Nigeria: implication for policy action

Background: Substance abuse among youths is fast becoming a global Public Health concern.
Objectives: This study assessed the prevalence and factors associated with substance abuse in selected public schools in Ogbomoso, South-West Nigeria.
Methods: Cross-sectional study design and multi-stage sampling method were utilized among 249 study participants who gave informed consent/assent. Data were collected using facilitated, self-administered questionnaire.Descriptive and inferential statistics using the Chi-Square test were carried out at p<0.05.
Results: The mean age of our respondents was 16.3±2SD; 40.0% of them had positive attitude to substance abuse while 21.7% had ever consumed alcoholic drinks. In all, 31(26.3%) of the respondents satisfied the criteria used in defining substance abuse.Tramadol was the most commonly abused substance apart from alcohol; reported by 39.0% of the substance abusers. Most (35.5%) of the substance abusers did so believing it could enhance their academic performance. The proportion of respondents who were substance abusers was significantly higher among students who had not received any formal lectures on the subject at school compared to those who had.(47.5% vs 29.7% ;p=0.023).
Conclusion: Our findings underscore an urgent need to intensify awareness against substance abuse among secondary school students in Nigeria.

Keywords: Substance abuse, youth, adolescents, attitude, secondary schools, Nigeria.

https://ift.tt/2BmGKZo

Effect of tramadol addiction alone and its co-abuse with cannabis on urinary excretion of Copper, Zinc, and Calcium among Egyptian addicts

Background: The use of illicit drugs has become a worldwide health problem. Substances with the potential to be abused may have direct or indirect effects on physiologic mechanisms that lead to organ system dysfunction and diseases.
Objective: The present study aims to investigate the structural and reabsorption integrity of the nephron among Egyptian addicts of tramadol alone and coabused with cannabis.
Methods: Sixty-five males were included in the study, they were classified into control group (G1=19), tramadol addicts group (G2=18), and tramadol coabused with cannabis addicts group (G3=28). Parameters investigated for structural integrity were urinary levels ofleucineaminopeptidase and N-acetyl-β-D-glucosaminidase, and urinary parameters for reabsorption integrity were levels of copper and zinc as well as calcium, also urinary creatinine was measured. In addition, urinary levels of tramadol and tetrahydrocannabinol were estimated.
Results: Among the two addicted groups, all measured parameters were not significantly different in comparison with the control group except for urinary calcium excretion which was found to be significantly increased among the two addicted groups.
Conclusion: Both tramadol addiction alone or coabused with cannabis causes increased urinary excretion of calcium, indicating reabsorption dysfunction of calcium without affecting structural integrity along the nephron.

Keywords: Enzymuria, copper, zinc, calcium, reabsorption impairment, tubular structural integrity.

https://ift.tt/2PleNEs

Under nutrition and associated factors among school adolescents in Dangila Town, Northwest Ethiopia: a cross sectional study

Background: Under nutrition in adolescents is an important determinant of health outcomes. Yet, adolescents are not usually part of health and nutrition surveys. Therefore, this research was conducted to assess factors associated with under nutrition among school adolescents.
Method: A cross-sectional study was conducted among 424 school adolescents from November 1-15, 2015. Simple random sampling was used to select the study participants. Data were collected using structured questionnaire and analyzed by SPSS version 20 software. Both bivariate and multivariable logistic regression analyses were carried out to identify predictors of under nutrition. Furthermore, anthropometric data were calculated using Anthro-plus software.
Result: The prevalence of stunting and thinness were 24.8 % and 7.1 %, respectively. Male gender [AOR=3.2, 95 % CI: (1.7, 5.8)], infrequent food intake [AOR=4.6, 95% CI: (2.6, 8.0)], unavailability of latrine [AOR=2.7, 95 % CI: (1.2, 6.0)], and poor hand washing practice [AOR=3.9, 95 % CI: (1.9, 8.1)] were independent predictors of stunting. Factors associated with thinness were being male [AOR=11.5, 95% CI: (3.3, 39.5)], illness in the last two weeks [AOR=2.9, 95 % CI: (1.2, 7.0)], and having more than five family members [AOR=3.6, 95% CI: (1.3, 9.4)].
Conclusion: The prevalence of under nutrition was high in this study. Infrequent food intake, unavailability of a latrine, poor hand washing practice, and large family members were the factors associated with under nutrition. There is need to implement nutrition education to school adolescents by giving emphasis on environmental and personal hygiene.

Keywords: Adolescent, stunting, thinness.

https://ift.tt/2BmGDwW

Nutrition knowledge, dietary patterns and anthropometric indices of older persons in four peri-urban communities in Ga West municipality, Ghana

Background: Older adults are vulnerable to malnutrition due to sociologic, physiologic and anatomical effects of ageing.
Objective: To investigate the influence of nutrition knowledge and dietary patterns on nutritional status of community-dwelling ambulatory older adults.
Methods: This cross-sectional survey involved 120 elderly aged 60-70 years purposively selected from four peri-urban communities in Ga West municipality, Ghana. Nutrition knowledge was assessed using a structured questionnaire and dietary intakes obtained using a standardized food frequency questionnaire. BMI from weight/height measurements was proxy for nutritional status. Data was analyzed descriptively in SPSS. Associations were tested using correlation analyses (-1<r<+1).
Results: 28% had adequate knowledge on geriatric nutrition. Dietary patterns were mostly fair (40%) or poor (53%). Bloating (25%), constipation (18%), appetite loss (12%) and chewing difficulties (11%) affected intakes. Underweight was 10% while 21.7% were overweight or obese (16.6%). Positive insignificant corrections existed between knowledge and nutritional status (r=0.261) and with diet quality (r=0.415). However, strong significant (p=0.027) positive correlation (r=0.699) existed between diet quality and nutritional status.
Conclusion: Nutrition knowledge was adequate but dietary intake was poor and a quarter were malnourished. The associations reaffirm that supporting the elderly to make healthy dietary choices and ensuring household food security is crucial to preventing malnutrition.

Keywords: Dietary knowledge, food diversity, body mass index, elderly, geriatric nutrition.

https://ift.tt/2PmkfXt

Vitamin A deficiency among under-five Nigerian children with diarrhoea

Background: Vitamin A deficiency (VAD) and diarrhoea are still important contributors to childhood deaths in Africa, and vitamin A deficient children are at increased risk as well as severity of diarrhoea.
Objectives:To determine the prevalence of VAD and identify the associated factors among children with diarrhoea.
Methods: The study was a hospital-based cross-sectional descriptive study. Consecutive children with diarrhoea were recruited, provided they met the inclusion criteria. Serum retinol levels were determined by high performance liquid chromatography (HPLC) in one hundred and seventy under-five children who presented with diarrhoea at the Wesley Guild Hospital, Ilesa, Nigeria.
Results: The serum retinol levels of the children ranged from 0.29 – 2.35 µmol/L with a mean ± SD of 1.07 ± 0.42 µmol/L. Twenty seven (15.9%) were vitamin A deficient with three (1.8%) of these having severe VAD. Wasting was significantly associated with a higher prevalence of VAD [p = 0.023, OR (95% CI) = 3.08 (1.21 - 7.79)]. A significantly greater proportion of the subjects who had VAD were hospitalized, compared with the non-deficient ones [p = 0.001, OR (95% CI) = 4.40 (1.82 - 10.66)]. The only subject who died was vitamin A deficient.
Conclusion: Wasting and hospitalization are factors that may indicate the presence of VAD in a child with diarrhoea. Vitamin A supplements should therefore be given, as part of the treatment for diarrhoea, to children who have wasting, especially when they require hospitalization.

Keywords: Vitamin A deficiency, Nigerian children, diarrhoea.

https://ift.tt/2BmGwBw

Status of thiocyanate levels in the serum and saliva of non-smokers, ex-smokers and smokers

Background: Use of tobacco is often implicated in the development of oral diseases. Questionable accuracy of the traditional questionnaires to assess cigarette exposure necessitates the use of biomarkers like thiocyanate which provide a definitive quantitative measure.
Objective: To assess the rise in the level of thiocyanate for measurement of smoking behaviour in adults.
Materials and methods: Serum and salivary thiocyanate levels were estimated in 20 non-smokers, 20 ex-smokers and 40 smokers. Smokers were divided into two groups based on the presence or absence of oral mucosal lesions.
Results: The mean serum and salivary thiocyanate levels were increased significantly in smokers when compared to non-smokers and ex-smokers. The levels were not significantly different between ex-smokers and non-smokers and between smokers with tobacco related oral mucosal lesions and those without. Statistically significant correlation was seen between the serum and salivary levels of thiocyanate.
Conclusion: This study highlights the high level of thiocyanate in the serum and saliva of smokers when compared to non-smokers and ex-smokers. Significant increase in thiocyanate level was also seen in saliva. Hence it can be stated that saliva can be used as a reliable, non-invasive tool to assess smoking behaviour in the population and its changes over time.

Keywords: Thiocyanate, tobacco, smoking, cancer, pre-cancer.

https://ift.tt/2MCzi0E

Association of serum asymmetric dimethyl-arginine and troponin I levels as a risk of myocardial infarction in thalassemia

Background: The current study evaluated level of serum asymmetric dimethylarginine (ADMA) and its association to cardiac biomarkers in thalassemia patients for early diagnosis of abnormality in myocardial infarction.
Subjects and methods: This study was conducted on 80 subjects divided into four groups each with 20 subjects. Group I: Control: healthy subjects. Group II: Myocardial infarction: Patients with elevated serum troponin T. Group III: thalassemia patients. Group IV: thalassemia with myocardial infarction patients: Included 20 thalassemia patients with Myocardial infarction. Serum samples were subjected for assay of creatine kinase (CK:MB), Lactate dehydrogenase, troponin I ,ADMA, Serum MDA level was determined.
Results: Data obtained showed that serum CKMB, LDH1, AST, Troponin T and ADMA levels were significant elevated in MI with or without Thalassemia compared with control groups. Serum MDA was statistically significantly elevated in MI with or without Thalassemia compared with control groups. The serum level of troponin T showed an area under curve (AUC) of 0.92 ,(sensitivity 91.0 % and specificity, 88%). Also, the ADMA supported the diagnostic profile, showing an AUC of 0.85 with (sensitivity, 92.0%; specificity, 91,9%).
Conclusion: Serum ADMA is sensitive marker for incidence of MI in thalassemia patients.

Keywords: CKMB, LDH1, AST, Troponin T, asymmetric dimethylarginie, Thalassemia.

https://ift.tt/2BpPM8e

Thyroid profile and LDH Isoenzymes as prognostic biomarkers for diabetic and/or obese subjects

Background: This study aimed to evaluate the levels of thyroid hormones and lactate dehydrogenase (LDH) isoenzymes in obese and/or diabetic patients.
Subjects and methods: Forty male subjects categorized into four equal groups; group 1: Non obese control subjects, group 2: Subjects suffering from type 2 diabetes mellitus (T2DM), group 3: Obese subjects (BMI ≥ 30 kg/m2) and group 4: Subjects thatwere obese and had type 2 diabetes mellitus (T2DM). Liver, kidney, lipid, thyroid hormones, total LDH and LDH isoenzymes levels were determined.
Results: There was a significant increase of TSH level (p<0.001) in diabetic group as compared with control group and a highly significant increase of TSH was obtained in obese and obese diabetic groups versus control and diabetic patients. LDH 2 was also highly significantly decreased in obese and obese diabetic groups versus diabetic patients. Percentage of LDH 4 was significantly decreased in both diabetic and obese groups and not significantly changed in obese diabetic patients as compared with the control group. LDH 5 percentage showed very highly significant decrease in diabetic, obese and highly significant decrease in obese diabetic groups when compared with control subjects while it was not significantly changed in obese and obese diabetic groups as compared with diabetic patients.
Conclusion: LDH isozymes can be used as valuable diagnostic markers for metabolic syndrome. This may help to explore the metabolic changes associated with obesity and diabetes complication and following up the complication of these abnormalities.

Keywords: Thyroid profile, lactate dehydrogenase, obesity, diabetes.

https://ift.tt/2MCzexW

Knowledge, attitude and practice towards cervical cancer among women in Finote Selam city administration, West Gojjam Zone, Amhara Region, North West Ethiopia, 2017

Introduction: Cancer of the cervix is the leading cause of cancer-related death among women, especially in developing countries affecting women at a time of life when they are critical to social and economic stability.
Method: The study was conducted at Finote Selam City Administration from February 01 to March 01, 2017 using a community-based cross-sectional study design. The representative sample size was selected using multistage sampling technique. The data were collected using an interviewer-administered questionnaire adapted from the previous study. Data were entered using EpiData Version 3.1 statistical software and analyzed using SPSS version 20 statistical package.
Result: One hundred seventy (23.1%) were knowledgeable about cervical cancer whereas 63% of participants had a negative attitude and only 7.3% had ever screened for the disease. Logistic regression analysis showed that age, marital status, religion, experienced sexual intercourse and age at 1st sexual intercourse were found to be significantly associated with the knowledge of cancer of the cervix.
Conclusion: Ministry of health in collaboration with other concerned bodies should design a strategy to give education about cervical cancer including information on risk factors, signs and symptoms; and availability of screening should be provided for women and as well as for the public.

Keywords: Cervical cancer, screening, Finote Selam, North West Ethiopia.

https://ift.tt/2BmGeuq

Development of a Comorbidity Index to Identify Patients With Small Bowel Bleeding at Risk for Rebleeding and Small Bowel Vascular Diseases

We aim to establish a comorbidity index for small bowel vascular diseases (SBVD) associated with small bowel bleeding (SBB) and recurrent bleeding.

https://ift.tt/2MCF4iX

Effects of Alfuzosin, an Alpha-1 Αdrenergic Antagonist on Anal Pressures and Bowel Habits, in Women With and Without Defecatory Disorders

Some patients with defecatory disorders (DD) have high anal pressures that may impede rectal evacuation. Αlpha-1 adrenoreceptors mediate as much as 50% of anal resting pressure in humans. We performed a randomized, placebo-controlled study of the effects of alfuzosin, an alpha1-adrenergic receptor antagonist, on anal pressures alone in healthy women and also on bowel symptoms in women with DD.

https://ift.tt/2BwmFQK

Pedunculated Morphology of T1 Colorectal Tumors Associates With Reduced Risk of Adverse Outcome

There have been no large-scale studies to compare pedunculated vs non-pedunculated T1 colorectal tumors; risk stratification for adverse events, such as metastasis to lymph nodes, is based only on histologic features of tumors. We aimed to compare adverse outcomes of pedunculated vs non-pedunculated T1 colorectal cancers (CRC).

https://ift.tt/2Mvp8iz

Changes in Renal Function in Patients With Chronic HBV infection Treated with Tenofovir Disoproxil Fumarate vs Entecavir

It is unclear whether drugs used to treat chronic hepatitis B virus (HBV) infection cause significant renal impairment. We compare adjusted mean estimated glomerular filtration rates (eGFR; mL/min/1.73 m2) of patients with chronic HBV infection treated with tenofovir disoproxil fumarate (TDF) vs patients treated with entecavir.

https://ift.tt/2wbMH5H

Low Referral Rate for Genetic Testing in Racially and Ethnically Diverse Patients Despite Universal Colorectal Cancer Screening

Guidelines recommend that all colorectal tumors be assessed for mismatch repair deficiency, which could increase identification of patients with Lynch syndrome. This is of particular importance for minority populations, in whom hereditary syndromes are under diagnosed. We compared rates and outcomes of testing all tumor samples (universal testing) collected from a racially and ethnically diverse population for features of Lynch syndrome.

https://ift.tt/2nLyCbs

PC-FACS: August 1, 2018

Giving Life-Expectancy Estimates

https://ift.tt/2OMc8SW

Pancreatic cancer: French Clinical Practice Guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC)

This document is a summary of the French Intergroup guidelines regarding the management of pancreatic adenocarcinoma (PA), updated in July 2018.

https://ift.tt/2OIeUbZ

Pitfalls in the reporting OF upper endoscopy features in cirrhotic patients

Upper endoscopy is the main tool for the accurate assessment of the risk of bleeding in cirrhotic patients.

https://ift.tt/2MGlJO5

Endoscopic findings and esophageal cancer incidence among Fanconi Anemia patients participating in an endoscopic surveillance program

WHAT IS CURRENT KNOWLEDGEWHAT IS NEW HERE

https://ift.tt/2OQGwvN

An Oligonucleotide-based Tandem RNA Isolation Procedure to Recover Eukaryotic mRNA-Protein Complexes

A tandem RNA isolation procedure (TRIP) for recovery of endogenously formed mRNA-protein complexes is described. Specifically, RNA-protein complexes are crosslinked in vivo, polyadenylated RNAs are isolated from extracts with oligo(dT) beads, and particular mRNAs are captured with modified RNA antisense oligonucleotides. Proteins bound to mRNAs are detected by immunoblot analysis.

https://ift.tt/2BmebLE

Quantification of Efferocytosis by Single-cell Fluorescence Microscopy

Efferocytosis, the phagocytic removal of apoptotic cells, is required to maintain homeostasis and is facilitated by receptors and signaling pathways that allow for the recognition, engulfment, and internalization of apoptotic cells. Herein, we present a fluorescence microscopy protocol for the quantification of efferocytosis and the activity of efferocytic signaling pathways.

https://ift.tt/2BkMQd1

Fusobacterium nucleatum promotes M2 polarization of macrophages in the microenvironment of colorectal tumours via a TLR4-dependent mechanism

Abstract

Fusobacterium nucleatum (Fn) has been shown to promote colorectal cancer (CRC) development by inhibiting host anti-tumour immunity. However, the impact of Fn infection on macrophage polarization and subsequent intestinal tumour formation as well as the underlying molecular pathways has not been investigated. We investigated the impact of Fn infection on macrophage polarization in human CRCs and cultured macrophages as well as the effects on macrophage phenotype and intestinal tumour formation in Apc^Min/+ mice. We also examined whether macrophage-polarized activation challenged by Fn infection via a TLR4-dependent mechanism involved the IL-6/STAT3/c-MYC signalling cascade. Our data showed that macrophages are a major tumour-infiltrating immune cell type in human CRCs with Fn infection (P < 0.001). Fn infection increased M2 polarization of macrophages in vitro and in vivo, leading to intestinal tumour growth in Apc^Min/+ mice. Moreover, Fn infection induced high expression of TLR4, IL-6, STAT3, p-STAT3, and c-MYC in cultured macrophages challenged with Fn, which was blocked by TAK-242 pre-treatment (P < 0.05). Interestingly, c-MYC protein was mainly co-localized with CD206⁺ M2 macrophages with Fn infection. In conclusion, we show that Fn infection increased M2 polarization of macrophages in vitro and in vivo. Furthermore, Fn infection enhanced colorectal tumour growth in a TLR4-dependent manner involving activation of the IL-6/p-STAT3/c-MYC signalling pathway. For the first time, our results indicate an immunosuppressive effect of Fn by promoting M2 polarization of macrophages through a TLR4-dependent mechanism, which may serve as a promising target for immunotherapy of Fn-related CRC.

https://ift.tt/2PfLPpk

Fusobacterium nucleatum promotes M2 polarization of macrophages in the microenvironment of colorectal tumours via a TLR4-dependent mechanism

Abstract

Fusobacterium nucleatum (Fn) has been shown to promote colorectal cancer (CRC) development by inhibiting host anti-tumour immunity. However, the impact of Fn infection on macrophage polarization and subsequent intestinal tumour formation as well as the underlying molecular pathways has not been investigated. We investigated the impact of Fn infection on macrophage polarization in human CRCs and cultured macrophages as well as the effects on macrophage phenotype and intestinal tumour formation in Apc^Min/+ mice. We also examined whether macrophage-polarized activation challenged by Fn infection via a TLR4-dependent mechanism involved the IL-6/STAT3/c-MYC signalling cascade. Our data showed that macrophages are a major tumour-infiltrating immune cell type in human CRCs with Fn infection (P < 0.001). Fn infection increased M2 polarization of macrophages in vitro and in vivo, leading to intestinal tumour growth in Apc^Min/+ mice. Moreover, Fn infection induced high expression of TLR4, IL-6, STAT3, p-STAT3, and c-MYC in cultured macrophages challenged with Fn, which was blocked by TAK-242 pre-treatment (P < 0.05). Interestingly, c-MYC protein was mainly co-localized with CD206⁺ M2 macrophages with Fn infection. In conclusion, we show that Fn infection increased M2 polarization of macrophages in vitro and in vivo. Furthermore, Fn infection enhanced colorectal tumour growth in a TLR4-dependent manner involving activation of the IL-6/p-STAT3/c-MYC signalling pathway. For the first time, our results indicate an immunosuppressive effect of Fn by promoting M2 polarization of macrophages through a TLR4-dependent mechanism, which may serve as a promising target for immunotherapy of Fn-related CRC.

https://ift.tt/2PfLPpk

Film Control to Study Contributions of Waves to Droplet Impact Dynamics on Thin Flowing Liquid Films

A protocol to study the contributions of waves to droplet impact dynamics on flowing liquid films is presented.

https://ift.tt/2OQeXTl

Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex

We have shown that a microelectrode implantation in the motor cortex of rats causes immediate and lasting motor deficits. The methods proposed herein outline a microelectrode implantation surgery and three rodent behavioral tasks to elucidate potential changes in the fine or gross motor function due to implantation-caused damage to the motor cortex.

https://ift.tt/2Mz01vi

UTILIZATION OF INJURY CARE CASE STUDIES: A SYSTEMATIC REVIEW OF THE WORLD HEALTH ORGANIZATION’S “STRENGTHENING CARE FOR THE INJURED: SUCCESS STORIES AND LESSONS LEARNED FROM AROUND THE WORLD”

Publication date: Available online 18 August 2018

Source: Injury

Author(s): Robert A. Tessler, Kathryn M. Stadeli, Witaya Chadbunchachai, Adam Gyedu, Lacey Lagrone, Teri Reynolds, Andres Rubiano, Charles N. Mock

ABSTRACT

Objective

Translation of evidence to practice is a public health priority. Worldwide, injury is a leading cause of morbidity and mortality. Case study publications are common and provide potentially reproducible examples of successful interventions in healthcare from the patient to systems level. However, data on how well case study publications are utilized are limited. To our knowledge, the World Health Organization (WHO) published the only collection of international case studies on injury care at the policy level. We aimed to determine the degree to which these injury care case studies have been translated to practice and to identify opportunities for enhancement of the evidence-to-practice pathway for injury care case studies overall.

Methods

We conducted a systematic review across 19 databases by searching for the title, "Strengthening care for the injured: Success stories and lessons learned from around the world." Data synthesis included realist narrative methods and two authors independently reviewed articles for injury topics, reference details, and extent of utilization.

Findings

Forty-seven publications referenced the compilation of case studies, 20 of which included further descriptions of one or more of the specific cases and underwent narrative review. The most common category utilized was hospital-based care (15 publications), with the example of Thailand's quality improvement (QI) programme (10 publications) being the most commonly cited case. Also frequently cited were case studies on prehospital care (10 publications). There was infrequent utilization of case studies on rehabilitation (3 publications) and trauma systems (2 publications). No reference described a case translated to a new scenario.

Conclusions

The only available collection of policy-level injury care case studies has been utilized to a moderate extent however we found no evidence of case study translation to a new circumstance. QI programmes seem especially amenable for knowledge-sharing through case studies. Prehospital care also showed promise. Greater emphasis on rehabilitation and health policy related to trauma systems is warranted. There is also a need for greater methodologic rigor in evaluation of the use of case study collections in general.

https://ift.tt/2PkLJg3

Response to letter to the editor by Moayyedi et al

We thank Moayyedi et al1 for their letter on our recent study investigating proton pump inhibitors (PPIs) on gastric cancer (GC) risk after Helicobacter pylori (HP) eradication.2 Although the association detected by an observational study may not mean causation, the possibility of causality can be strengthened by fulfilling the Bradford Hill criteria. In our study, these include strength (HR: 2.43), specificity (stomach is the only organ that PPIs may impose a cancer risk), temporality (all GC cases developed after triple therapy), biological gradient (dose and duration response relationship shown), plausibility (worsening of preneoplastic gastric changes and bacterial overgrowth under profound acid suppression), experiment (as illustrated in animal model studies) and analogy (achlorhydria due to autoimmune gastritis causes GC).

Concerns were raised over inadequate adjustment for socioeconomic status and comorbidities. Hong Kong is a highly urbanised city with excellent sanitation and easily accessible healthcare services. Hence, socioeconomic status is likely a negligible concern....

https://ift.tt/2L53sVt

Switchable CAR-T cells mediate remission in metastatic pancreatic ductal adenocarcinoma

Objective

Pancreatic ductal adenocarcinoma (PDAC) is a disease of unmet medical need. While immunotherapy with chimeric antigen receptor T (CAR-T) cells has shown much promise in haematological malignancies, their efficacy for solid tumours is challenged by the lack of tumour-specific antigens required to avoid on-target, off-tumour effects. Switchable CAR-T cells whereby activity of the CAR-T cell is controlled by dosage of a tumour antigen-specific recombinant Fab-based 'switch' to afford a fully tunable response may overcome this translational barrier.

Design

In this present study, we have used conventional and switchable CAR-T cells to target the antigen HER2, which is upregulated on tumour cells, but also present at low levels on normal human tissue. We used patient-derived xenograft models derived from patients with stage IV PDAC that mimic the most aggressive features of PDAC, including severe liver and lung metastases.

Results

Switchable CAR-T cells followed by administration of the switch directed against human epidermal growth factor receptor 2 (HER2)-induced complete remission in difficult-to-treat, patient-derived advanced pancreatic tumour models. Switchable HER2 CAR-T cells were as effective as conventional HER2 CAR-T cells in vivo testing a range of different CAR-T cell doses.

Conclusion

These results suggest that a switchable CAR-T system is efficacious against aggressive and disseminated tumours derived from patients with advanced PDAC while affording the potential safety of a control switch.

https://ift.tt/2PjMfuM

Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: a study within the National Cancer Institute Cohort Consortium

Objective

Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk.

Design

This nested case–control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls from seven prospective cohort studies. We quantitated 69 circulating inflammation markers using Luminex-based multiplex assays. Conditional logistic regression models estimated associations between inflammation markers and oesophageal adenocarcinoma, as well as direct and indirect effects of obesity and smoking on risk of malignancy.

Results

Soluble tumour necrosis factor receptor 2 (sTNFR2) (ORs_{quartile 4 vs 1}=2.67, 95% CI 1.52 to 4.68) was significantly associated with oesophageal adenocarcinoma. Additional markers close to the adjusted significance threshold included C reactive protein, serum amyloid A, lipocalin-2, resistin, interleukin (IL) 3, IL17A, soluble IL-6 receptor and soluble vascular endothelial growth factor receptor 3. Adjustment for body mass index, waist circumference or smoking status slightly attenuated biomarker–cancer associations. Mediation analysis indicated that sTNFR2 may account for 33% (p=0.005) of the effect of waist circumference on oesophageal adenocarcinoma risk. Resistin, plasminogen activator inhibitor 1, C reactive protein and serum amyloid A were also identified as potential mediators of obesity–oesophageal adenocarcinoma associations. For smoking status, only plasminogen activator inhibitor 1 was a nominally statistically significant (p<0.05) mediator of cancer risk.

Conclusion

This prospective study provides evidence of a link between systemic inflammation and oesophageal adenocarcinoma risk. In addition, this study provides the first evidence that indirect effects of excess adiposity and cigarette smoking, via systemic inflammation, increase the risk of oesophageal adenocarcinoma.

https://ift.tt/2L5iU3T

Alcohol inhibits T-cell glucose metabolism and hepatitis in ALDH2-deficient mice and humans: roles of acetaldehyde and glucocorticoids

Objective

Aldehyde dehydrogenase 2 (ALDH2), a key enzyme to detoxify acetaldehyde in the liver, exists in both active and inactive forms in humans. Individuals with inactive ALDH2 accumulate acetaldehyde after alcohol consumption. However, how acetaldehyde affects T-cell hepatitis remains unknown.

Design

Wild-type (WT) and Aldh2 knockout (Aldh2 ^-/-) mice were subjected to chronic ethanol feeding and concanavalin A (ConA)-induced T-cell hepatitis. Effects of acetaldehyde on T-cell glucose metabolism were investigated in vitro. Human subjects were recruited for binge drinking and plasma cortisol and corticosterone measurement.

Results

Ethanol feeding exacerbated ConA-induced hepatitis in WT mice but surprisingly attenuated it in Aldh2 ^-/- mice despite higher acetaldehyde levels in Aldh2 ^-/- mice. Elevation of serum cytokines and their downstream signals in the liver post-ConA injection was attenuated in ethanol-fed Aldh2 ^-/- mice compared to WT mice. In vitro exposure to acetaldehyde inhibited ConA-induced production of several cytokines without affecting their mRNAs in mouse splenocytes. Acetaldehyde also attenuated interferon- production in phytohaemagglutinin-stimulated human peripheral lymphocytes. Mechanistically, acetaldehyde interfered with glucose metabolism in T cells by inhibiting aerobic glycolysis-related signal pathways. Finally, compared to WT mice, ethanol-fed Aldh2 ^-/- mice had higher levels of serum corticosterone, a well-known factor that inhibits aerobic glycolysis. Blockade of corticosterone partially restored ConA-mediated hepatitis in ethanol-fed Aldh2 ^-/- mice. Acute alcohol drinking elevated plasma cortisol and corticosterone levels in human subjects with higher levels in those with inactive ALDH2 than those with active ALDH2.

Conclusions

ALDH2 deficiency is associated with elevated acetaldehyde and glucocorticoids post-alcohol consumption, thereby inhibiting T-cell activation and hepatitis.

https://ift.tt/2vVwAtD

Chemo-Radiation After Upfront Rectal Resections—a Clinical Dilemma

Abstract

To compare the impact of adjuvant chemo-radiotherapy (ACRT) versus adjuvant chemotherapy (ACT) alone on recurrence and survival in patients with stage II and III rectal adenocarcinoma undergoing upfront curative resection. Prospective observational review of colorectal database at Tata Memorial Hospital from July 2010 to March 2015 identified 84 patients who underwent upfront curative resection for stage II or III rectal cancer. None of the patient received preoperative chemo-radiation. Of these, adjuvant chemo-radiotherapy was administered to 29 patients (ACRT group) and 55 patients received CAPEOX/FOLFOX-based adjuvant chemotherapy (ACT group) alone. At a median follow-up of 20 months, there were 10 recurrences (3 local recurrence) in the ACRT group and 15 (2 local recurrence) in ACT group. The estimated disease-free survival at 3 years in the ACRT group was 62.7% and in ACT group was 49.7% (p = 0.417) with an estimated 3-year overall survival of 74 and 78% in the ACRT and ACT group, respectively (p = 0.241). Subgroup analysis was performed after risk stratifying prognostic features (pT4, pN2, poor differentiation, involved resection margin). Our study does not show any benefit of ACRT over ACT on local control, disease-free and overall survival after upfront rectal cancer resection for low-risk stage II–III. In the subgroup analysis, local recurrence did not occur in patients who did not have poor prognostic features irrespective whether they received ACRT or ACT. Adjuvant chemo-radiation can be avoided in low-risk stage II–III rectal cancer after upfront resection.

https://ift.tt/2L3ZFYE

Role of intensive nutrition support and prophylactic percutaneous endoscopic gastrostomy during concomitant chemoradiotherapy for oropharyngeal cancer

Abstract

Background

Concomitant chemoradiotherapy (CCRT) produces severe mucositis and swallowing dysfunction, often resulting in malnutrition. Intensive nutrition support (INS) in addition to percutaneous endoscopic gastrostomy (PEG) is reported to decrease adverse effects during CCRT.

Patients and Methods

Fifty-eight patients with oropharyngeal cancer treated by CDDP-based CCRT were retrospectively analyzed. Twenty-nine patients treated with INS in addition to PEG were classified as INS group, and other 29 patients treated with PEG but without INS were classified as control group.

Results

INS in addition to PEG significantly increased calorie intake in the second half of CCRT and reduced adverse events including mucositis (p = 0.0019), leukopenia (p = 0.04), and renal function (p = 0.006). Moreover, 21 out of 29 patients had successfully administration of 200 mg/m2 or more of CDDP, while only 10 out of 29 patients had enough amount of CDDP in control group.

Conclusions

These results suggest that INS in addition to prophylactic PEG not only decreases adverse effects but also may potentially improve oncological outcome of the patients with oropharyngeal cancer treated by CCRT.

https://ift.tt/2MCd0MD

South Korea: in the midst of a privacy reform centered on data sharing

Abstract

With rapid developments in genomic and digital technologies, genomic data sharing has become a key issue for the achievement of precision medicine in South Korea. The legal and administrative framework for data sharing and protection in this country is currently under intense scrutiny from national and international stakeholders. Policymakers are assessing the relevance of specific restrictions in national laws and guidelines for better alignment with international approaches. This manuscript will consider key issues in international genome data sharing in South Korea, including consent, privacy, security measures, compatible adequacy and oversight, and map out an approach to genomic data sharing that recognizes the importance of patient engagement and responsible use of data in South Korea.

https://ift.tt/2nNhfqw

Thioredoxin overexpression in both the cytosol and mitochondria accelerates age-related disease and shortens lifespan in male C57BL/6 mice

Abstract

To investigate the role of increased levels of thioredoxin (Trx) in both the cytosol (Trx1) and mitochondria (Trx2) on aging, we have conducted a study to examine survival and age-related diseases using male mice overexpressing Trx1 and Trx2 (TXNTg × TXN2Tg). Our study demonstrated that the upregulation of Trx in both the cytosol and mitochondria in male TXNTg × TXN2Tg C57BL/6 mice resulted in a significantly shorter lifespan compared to wild-type (WT) mice. Cross-sectional pathology data showed a slightly higher incidence of neoplastic diseases in TXNTg × TXN2Tg mice than WT mice. The incidence of lymphoma, a major neoplastic disease in C57BL/6 mice, was slightly higher in TXNTg × TXN2Tg mice than in WT mice, and more importantly, the severity of lymphoma was significantly higher in TXNTg × TXN2Tg mice compared to WT mice. Furthermore, the total number of histopathological changes in the whole body (disease burden) was significantly higher in TXNTg × TXN2Tg mice compared to WT mice. Therefore, our study suggests that overexpression of Trx in both the cytosol and mitochondria resulted in deleterious effects on aging and accelerated the development of age-related diseases, especially cancer, in male C57BL/6 mice.

https://ift.tt/2OKPxWO

Prefrontal activation during Stroop and Wisconsin card sort tasks in children with developmental coordination disorder: a NIRS study

Abstract

We used near-infrared spectroscopy to examine dorsolateral prefrontal cortex (DLPFC) activation over time in 10 children with or at-risk-for developmental coordination disorder (DCD) and 11 typically developing children (ages 8–12) during tasks involving executive processing. The groups performed with similar accuracy on the Stroop and Wisconsin card sort (WCST), but their underlying neural activation differed. Typically developing children modulated DLPFC activity over time and showed rightward lateralization during Stroop but no lateralization during WCST. The DCD group exhibited high and sustained activation across hemispheres and tasks, which we suggest is a compensatory effort to maintain response accuracy.

https://ift.tt/2PhE2aC

Leptin is a physiological regulator of skeletal muscle angiogenesis and is locally produced by PDGFRα and PDGFRβ expressing perivascular cells

Abstract

Skeletal muscle capillarity is characteristically reduced in mature leptin receptor-deficient (Lepr^db) mice, which has been attributed to the capillary loss that occurs secondary to metabolic dysfunction. Despite wide recognition of leptin as a pro-angiogenic molecule, the contribution of this adipokine has largely been overlooked in peripheral tissues. Moreover, prior documentation of leptin production within skeletal muscle indicates a potential paracrine role in maintaining local tissue homeostasis. Thus, we hypothesized that leptin is a physiological local paracrine regulator of skeletal muscle angiogenesis and that its production may be modulated by nutrient availability. Lepr^db mice exhibited impaired angiogenesis during normal developmental maturation of skeletal myocytes, corresponding with an inability to increase vascular endothelial growth factor-A (VEGFA) mRNA and protein levels between 4 and 13 weeks. In cultured murine and human skeletal myocytes, recombinant leptin increased VEGFA mRNA levels. Leptin mRNA was detectable in skeletal muscle, increasing with prolonged high-fat feeding in mice, and with adiposity in human subjects. Platelet-derived growth factor receptor (PDGFR)α− and PDGFRβ− expressing perivascular cell populations were identified as leptin producing within skeletal muscle of mice and humans. Furthermore, in response to 2 weeks of high-fat feeding, PDGFRβ+ but not PDGFRα+ cells increased leptin production. We conclude that leptin is a physiological regulator of the capillary network in skeletal muscle and stimulates VEGFA production by skeletal myocytes. PDGFRβ expressing perivascular cells exhibit the capacity to act as local "nutrient-sensors" that couple nutrient status to leptin production in skeletal muscle.

https://ift.tt/2vQCiNq

Next-generation sequencing reveals mutational accordance between cell-free DNA from plasma, malignant pleural effusion and ascites and directs targeted therapy in a gastric cancer patient

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https://ift.tt/2nLhiDp

Does a fixed offset hemiarthroplasty implant have any effect on pain and function in patients with a femoral neck fracture?

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): Bola Akinola, Ruaraidh Collins, Francis C.J. Sim, Martyn J. Parker

Abstract

Introduction

Hip hemiarthroplasty is the commonest operation performed for a displaced intracapsular hip fracture in the UK. A variety of implants including fixed offset prostheses are utilised. There has been no study investigating the relationship between restoration of femoral offset and long term pain and function. This study aims to evaluate long-term pain and functional outcomes of a fixed offset hemiarthroplasty implant (the Exeter trauma system).

Patients and methods

All patients were retrospectively reviewed from a prospectively collected database. In all, 338 patients met the criteria for evaluation. Patients native offset were calculated from the contralateral hip. Pain and functional outcomes were assessed using validated outcome measures.

Results

There were no differences found across a range of natural offsets for long-term pain and functional recovery.

Conclusion

Our experience with the Exeter trauma system suggests that a 40 mm offset implant is a good standard offset to use.

https://ift.tt/2MFvfkx

Early postoperative hypoalbuminemia is a risk factor for postoperative acute kidney injury following hip fracture surgery

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): Kyun-Ho Shin, Seung-Beom Han

Abstract

Introduction

Acute kidney injury (AKI) is a common and serious complication after hip fracture surgery in older adults. Hypoalbuminemia is a known independent risk factor for AKI. However, few studies have investigated the relationship between early postoperative hypoalbuminemia and AKI after hip fracture surgery. Therefore, we sought to determine the incidence of and risk factors for AKI and the effects of early postoperative hypoalbuminemia on AKI incidence after surgery for hip fractures, especially intertrochanteric fractures of the proximal femur.

Patients and methods

In this retrospective cohort study from a single center, we reviewed the medical records of 481 consecutive patients (>60 years) who underwent surgery for intertrochanteric fracture of the proximal femur. Multiple logistic regression was performed to identify independent risk factors for AKI. After determining the cut-off value of the minimal level of postoperative serum albumin during the first two postoperative days, we divided the patients into two groups: group 1 included 251 patients whose minimal early postoperative serum albumin level was <2.9 g/dL during the first two postoperative days; and group 2 included 230 patients whose minimal early postoperative serum albumin level was ≥2.9 g/dL. The incidence of AKI was analyzed using inverse probability of treatment weighting (IPTW), propensity score matching (PSM), and propensity score matching weighting (PSMW) analyses.

Results

The incidence of AKI, defined based on the Kidney Disease Improving Global Outcomes criteria, was 11.8% (n = 57). Chronic kidney disease and the minimal early postoperative serum albumin level <2.9 g/dL at any point during the first two postoperative days were independent risk factors for AKI. The IPTW, PSM, and PSMW analyses comparing the incidence of AKI between the two groups revealed that the minimal early postoperative serum albumin level <2.9 g/dL was significantly associated with AKI development (P < 0.001, P = 0.025, and P = 0.011, respectively).

Conclusion

The incidence of postoperative AKI was 11.8%. Our findings demonstrate that early postoperative hypoalbuminemia is an independent risk factor for AKI in patients undergoing surgery for intertrochanteric fracture of the proximal femur.

https://ift.tt/2OMqSRJ

Iatrogenic fracture gapping during fixation of Jones fractures: Anatomic and mechanical considerations in a cadaveric model

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): Philip B. Kaiser, Matthew D. Riedel, Rameez A. Qudsi, Mohammad Ghorbanhoseini, John Y. Kwon

Abstract

Background

Surgical fixation of Jones fractures is often recommended to facilitate recovery and achieve union. Iatrogenic fracture displacement during intramedullary screw fixation is a commonly encountered technical issue. This may be related to fracture location in relation to the surrounding ligamentous attachments, namely the robust intermetatarsal ligaments found at the proximal articulation of the 4th and 5th metatarsals. This study examines the relationship between fracture line and its location in regards to the surrounding ligamentous structures and its effect on Jones fracture displacement, reduction and fixation in a cadaveric model.

Methods

Eighteen fresh-frozen cadaveric feet were dissected with preservation of all ligamentous attachments. Given the similar anatomic distal extent of the dorsal and plantar intermetatarsal ligaments on the 5th metatarsal, measurements were obtained detailing the anatomic position of the dorsal intermetatarsal ligament (DIL) only. The specimens were divided into two groups with modelled fractures created at the 4th & 5th metatarsal articulation proximal to the distal extent of the DIL (Group 1) or just distal to the DIL (Group 2). Fractures were fixed in standard fashion with serial fluoroscopic images obtained to study fracture gapping and rotation.

Results

There was approximately 5 mm of fracture gapping created iatrogenically during tapping with no statistically significant differences between Group 1 and Group 2 (4.53 mm versus 5.25 mm, p = 0.5430). The distal aspect of the DIL was anatomically located 2.77 mm (Range 1.58 mm–4.46 mm) distal to the 4th & 5th metatarsal articulation.

Conclusions

Considerable iatrogenic fracture gapping occurs during intramedullary screw fixation of Jones fractures in a cadaveric model regardless of fracture location in relation to the intermetatarsal ligamentous attachments. Specific techniques may be required to maintain anatomic alignment during tapping and screw fixation to prevent iatrogenic displacement.

Level of evidence

V, Expert Opinion.

https://ift.tt/2MFv9tb

Beagle sciatic nerve regeneration across a 30 mm defect bridged by chitosan/PGA artificial nerve grafts

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): Ye Peng, Kai-Yuan Li, Yu-Fei Chen, Xiao-Jie Li, Shu Zhu, Zheng-Yu Zhang, Xiao Wang, Li-Na Duan, Zhuo-Jing Luo, Jun-Jie Du, Jian-Chang Wang

Abstract

Longitudinally oriented microstructures are essential for a nerve scaffold to promote the significant regeneration of injured peripheral axons across nerve gaps. In the current study, we present a novel nerve-guiding collagen-chitosan (CCH) scaffold that facilitated the repair of 30 mm-long sciatic nerve defects in beagles. The CCH scaffolds were observed with a scanning electron microscope. Eighteen beagles were equally divided into CCH group, autograft group and non-graft group. The posture and gait of each dog was recorded at 12 and 24 weeks after surgery. Electrophysiological tests, Fluoro-Gold retrograde tracing test, Histological assessment of gastrocnemius and immunofluorescent staining of nerve regeneration were performed. Our investigation of regenerated sciatic nerves indicated that a CCH scaffold strongly supported directed axon regeneration in a manner similar to that achieved by autologous nerve transplantation. In vivo animal experiments showed that the CCH scaffold achieved nerve regeneration and functional recovery equivalent to that achieved by an autograft but without requiring the exogenous delivery of regenerative agents or cell transplantation. We conclude that CCH nerve guides show great promise as a method for repairing peripheral nerve defects.

https://ift.tt/2OLgEB9

Identifying research priorities around psycho-cognitive and social factors for recovery from hip fractures: An international decision-making process

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): Mohammad Auais, Simon D. French, Lauren Beaupre, Lora Giangregorio, Jay Magaziner

Abstract

Hip fractures rank in the top ten disabling conditions worldwide. With an ageing population, this public health problem is expected to increase. Despite the success of surgery for hip fractures and the extensive health services utilisation, health outcomes are often poor. Considering the recovery process as multifactorial and intervening to address all relevant factors may improve recovery rates. However, we need first to fully understand the factors contributing to recovery after hip fractures, including psycho-cognitive and social factors. The purpose of this study was to identify future research priorities for understanding the role of psycho-cognitive and social factors in the recovery process for community-dwelling older adults after hip fracture and to survey world experts to confirm the identified priorities.

Methods

This was a two-stage process. First, a workshop of international experts in hip fracture care (researchers and clinician-scientists) was held in 2016 in Montreal, Quebec, Canada. Using Nominal Group Technique accompanied by Multi-voting Technique, workshop attendees identified the most important future research areas for psycho-cognitive and social factors contributing to recovery after hip fractures. Second, an online survey of the International Fragility Fracture Network (FFN), which includes researchers and clinicians interested in fragility fractures, followed the meeting. The survey respondents reviewed and added to priorities from the first stage and then ranked the top priorities.

Results

Twenty-three experts participated in the meeting (from five countries) and 152 participants (from 29 countries) responded to the survey. Top priorities for the psycho-cognitive domain were preventing and treating in-hospital delirium; comparing the effectiveness of targeted versus multifactorial interventions; studying interactions between psycho-cognitive, social, and environmental factors in the recovery process; and modifying the environment to enhance patients' cognitive reserves. Top priorities for the social domain were understanding the role of social factors in the recovery process; understanding patients' perspectives on important social factors; identifying components of social support relevant to recovery; understanding attitudes towards patients with hip fractures among all stakeholders; and understanding the social support needs for caregivers.

Conclusion

A set of future research priorities to understand the role of psycho-cognitive and social factors has been developed and confirmed through a rigorous international decision-making process. These priorities offer valuable guidance for researchers, scientific bodies, and funding agencies.

https://ift.tt/2Mx4fDz

The biology of fracture healing in osteoporosis and in the presence of anti-osteoporotic drugs

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): David J. Hak

Abstract

Compromised bone strength in osteoporosis predisposes patients to an increased fracture risk. The management of these fractures is complicated due to the poor bone quality, which may lead to inadequate fixation strength and stability. While a number of studies using osteoporotic animal models have shown a detrimental impact on fracture healing, clinical evidence regarding whether fracture healing is impaired in the presence of osteoporosis is complicated by numerous associated conditions including advancing age.

The mechanism of some anti-osteoporotic medications creates concern about a potential detrimental impact on fracture healing, while others appear to enhance fracture healing. The current evidence indicates that the beneficial effects of anti-osteoporosis treatment exceeds any concerns about possible adverse consequences on fracture healing in most circumstances.

https://ift.tt/2OO2ZcN

Epidemiology and social costs of hip fracture

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): Nicola Veronese, Stefania Maggi

Abstract

Hip fracture is an important and debilitating condition in older people, particularly in women. The epidemiological data varies between countries, but it is globally estimated that hip fractures will affect around 18% of women and 6% of men. Although the age-standardised incidence is gradually falling in many countries, this is far outweighed by the ageing of the population. Thus, the global number of hip fractures is expected to increase from 1.26 million in 1990 to 4.5 million by the year 2050. The direct costs associated with this condition are enormous since it requires a long period of hospitalisation and subsequent rehabilitation. Furthermore, hip fracture is associated with the development of other negative consequences, such as disability, depression, and cardiovascular diseases, with additional costs for society.

In this review, we show the most recent epidemiological data regarding hip fracture, indicating the well-known risk factors and conditions that seem relevant for determining this condition. A specific part is dedicated to the social costs due to hip fracture. Although the costs of hip fracture are probably comparable to other common diseases with a high hospitalisation rate (e.g. cardiovascular disease), the other social costs (due to onset of new co-morbidities, sarcopenia, poor quality of life, disability and mortality) are probably greater.

https://ift.tt/2Mx43UR

Cement augmentation of the Proximal Femoral Nail Antirotation (PFNA) – A multicentre randomized controlled trial

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): Christian Kammerlander, Einar S. Hem, Tim Klopfer, Florian Gebhard, An Sermon, Michael Dietrich, Olaf Bach, Yoram Weil, Reto Babst, Michael Blauth

Abstract

Introduction

New implant designs like the Proximal Femoral Nail Antirotation (PFNA) were developed to reduce failure rates in unstable pertrochanteric fractures in the elderly. Standardized implant augmentation with up to 6 mL of polymethylmethacrylate (PMMA) cement has been introduced to enhance implant anchorage by increasing the implant-bone interface in osteoporotic bone conditions. Biomechanically, loads to failure were significantly higher with augmentation. The primary objective of this study was to compare the mobility of patients with closed unstable trochanteric fractures treated by PFNA either with or without cement augmentation.

Patients and methods

A prospective multicentre, randomized, patient-blinded trial was conducted with ambulatory patients aged 75 or older who sustained a closed, unstable trochanteric fracture. Surgical fixation had to be performed within 72 h after admission. Outcomes were evaluated at baseline, during surgery, 3 to 14 days after surgery, 3 months, 6 months, and 12 months after surgery. To evaluate the primary objective, patients' walking speed was assessed by the Timed Up and Go (TUG) test. Secondary objectives included the analysis of implant migration assessed on radiographs, quality of life measured by the Barthel Index, mobility measured by the Parker Mobility Score, and complications.

Results

Of 253 randomized patients, 223 patients were eligible: 105 patients were allocated to the PFNA Augmentation group and 118 to PFNA group. At 3 to 14 days after surgery, there was no statistical significant difference in mean walking speed between the treatment groups. For the secondary objectives, also no statistical significant differences were found. However, no patient in the PFNA Augmentation group had a reoperation due to mechanical failure or symptomatic implant migration compared to 6 patients in the PFNA group.

Conclusions

Augmentation of the PFNA blade did not improve patients' walking ability compared to the use of a non-augmented PFNA but might have the potential to prevent reoperations by strengthening the osteosynthesis construct.

https://ift.tt/2BmYHHm

Vertebral Fragility Fractures (VFF)—Who, when and how to operate

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): Opinder Sahota, Terence Ong, Khalid Salem

Abstract

Vertebral Fragility Fractures (VFF) are common and lead to pain, long term disability and increased mortality. Most patients will have mild to moderate pain symptoms and can be managed conservatively. However, patients with severe pain who have minimal or no pain relief with potent analgesia, or who only achieve adequate pain relief with high doses of morphine based analgesia which results in significant adverse events, should be considered for vertebral augmentation. Ideally, for vertebral augmentation, patients should present within four months of the fracture (onset of acute pain) and have at least 3 weeks of failure of conservative treatment although early intervention may be more appropriate for hospitalised patients, who tend to be older, more frail and likely to be less tolerant to the adverse effects of conservative treatment.

The Cardiovascular and Interventional Radiological Society of Europe (CIRSE) recommends Percutaneous Vertebroplasty as the first line surgical augmentation technique for VFF in older people, which has been shown to improve pain symptoms, allow early restoration of functional mobility and may reduce the risk of further vertebral collapse. CIRSE recommends percutaneous Balloon Kyphoplasty as second line treatment in VFF, although the optimal indication is for acute traumatic vertebral fractures (less than 7–10 days) in younger people. Assessment and treatment of underlying osteoporosis is important to reduce the risk of further fractures in older people with VFF.

https://ift.tt/2MxCRp8

Orthogeriatric co-management – managing frailty as well as fragility

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): Giulio Pioli, Chiara Bendini, Paolo Pignedoli, Andrea Giusti, David Marsh

Abstract

A high proportion of patients with fragility fracture, mainly hip fracture, have a variable degree of comorbidity and show some degree of dependence in basic or more complex activities of daily living. Evaluating these patents following the geriatric concept of frailty, about one third of hip fracture patients may be categorised as frail with high risk of poor outcomes and prolonged length of stay, one third as not frail, and about one third with an intermediate condition. Due to the high vulnerability, combined with the hip fracture event and surgical repair procedures, a multidisciplinary approach that includes geriatric competencies becomes essential to improve short and long-term outcomes after hip fracture. A key element of an effective process of care is a true co-managed approach that applies quality standards and provides a fast-track pathway of care, minimises the time the patient spends in bed, and reduces postoperative complications by means of standardised procedures.

The occurrence of a fragility fracture is the strongest risk factor for a subsequent fracture. Moreover, frail subjects have a further risk of fracture due to high risk of falls − related to loss of muscle mass, multiple illnesses, impaired balance and weakness. Thus, effective secondary prevention strategies are essential to reduce morbidity and mortality after hip fracture, and they are currently a standard task of orthogeriatric care. Fracture liaison services (FLS) are probably the most efficient way of addressing secondary prevention including the assessment of both bone health and falls risk. Therefore, the optimal management of frail patients with fragility fracture includes both orthogeriatric care and FLS, which are complementary to each other.

Orthogeriatric collaboration is also powerful in influencing healthcare policy. British experience as well as that in Ireland, Australia and New Zealand, have shown that when two widely disparate specialisms say the same thing, they may achieve a fundamental shift in attitudes and behaviour of both managers and clinicians. Furthermore, a continuous real-time audit, at national level, is a powerful driver for change and better standards of care.

https://ift.tt/2Bn5Fw1

Bone augmentation: Is it really needed?

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): Joey P. Johnson, Grayson Norris, Peter V. Giannoudis

https://ift.tt/2MEBDIM

Editorial Board/Publication Information

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s):

https://ift.tt/2OLFtNp

Variables affecting functional outcome in floating knee injuries

Publication date: August 2018

Source: Injury, Volume 49, Issue 8

Author(s): Mahesh Suresh Kulkarni, Monappa Naik Aroor, Sandeep Vijayan, Saurabh Shetty, Sujit Kumar Tripathy, Sharath K Rao

Abstract

Background

The surgical outcome of floating knee injuries is difficult to predict. The high-velocity nature of the injury, complex fracture pattern and associated soft tissue/visceral injuries may have some impact on the functional outcome. The present study evaluates the variables affecting the clinical and radiological outcomes of floating knee injuries.

Materials and methods

The clinical, radiological and functional outcome (Karlstrom and Olegrud criteria) of 89 patients with 90 floating knee injuries were evaluated at the end of one year who were managed in our level 1 trauma center between January 2013 and December 2016. The details of the injury, fracture pattern, management and complications were collected retrospectively from their records.

Results

There were 81 (91.1%) males and 8 (8.9%) females with mean age of 34.34 ± 12.28 years. The mean time for tibia and femur union was 9.52 (±6.6) and 10.5 (±7.37) months. There was significant delay (p < 0.005) in time taken for union in segmental femur fractures (14.3 ± 9.6 months) compared to nonsegmental femur fractures (8.68 ± 5.18 months). Such significant difference in time taken for union was not seen in tibial segmental (10.6 ± 4.62 months) and nonsegmental fractures (9.05 ± 7.27 months). As per the Karlstrom and Olegrud criteria, there were 22 (24.4%) excellent, 26 (28.9%) good, 24 (26.7%) fair and 11 (12.2%) poor outcome. There were 15 patients with malunited tibia, 6 with malunited femur, 10 with limb length discrepancy and 39 with knee stiffness. 28 (33.3%) patients underwent major additional procedures such as bone grafting, re-fixation or bone transport or tendon transfer. It was observed that open tibia fracture, segmental fracture, intra-articular fracture, additional surgical procedures, initial external-fixator (ex-fix) application were significantly associated with development of knee stiffness, limb shortening, malalignment and unsatisfactory (Karlstrom and Olegrud fair to poor) functional outcome.

Conclusion

Open tibial fractures, segmental fractures, intraarticular involvement, additional surgical procedures and initial external fixator application are the poor prognostic indicators of floating knee injuries.

https://ift.tt/2MweXKp

Cellular-based immunotherapy in Epstein-Barr virus induced nasopharyngeal cancer.

Related Articles

Cellular-based immunotherapy in Epstein-Barr virus induced nasopharyngeal cancer.

Oral Oncol. 2018 Sep;84:61-70

Authors: Lee AZE, Tan LSY, Lim CM

Abstract
Undifferentiated Nasopharyngeal carcinoma (NPC) is ubiquitously identified with the Epstein-Barr virus (EBV), making this cancer a suitable candidate for cellular-based immunotherapy (CBI) due to its expression of potentially targetable tumor-associated viral antigens. Various preclinical and clinical studies have explored the use of cytotoxic T cells (CTLs), tumor-infiltrating lymphocytes (TILs), natural killer (NK) cells, and dendritic cells (DCs) in the treatment of both refractory and locally advanced NPC with some success. Notably, immune-mediated antitumor effects were observed even in heavily pre-treated NPC patients, suggesting potential clinical benefit of CBI in this group of patients. These immune anti-tumor effects may be even more clinically evident when used as a first-line treatment, since there may not be an intense immunosuppressive environment which is typically encountered in refractory cancer patients. Additionally, CBI may exert an effect in priming the immune system and diminishing the cancer's acquired resistance to exert a more robust response to previously failed chemotherapy. Although these results are encouraging, further refinements of clinical protocols to boost anti-tumor response and benefit a larger subset of patients proved necessary. Herein, we aim to review the rational of developing CBI in EBV-induced NPC and summarize its current applications in clinical studies.

PMID: 30115477 [PubMed - in process]

https://ift.tt/2vV6jvx

Cancers, Vol. 10, Pages 274: Genetics and Expression Profile of the Tubulin Gene Superfamily in Breast Cancer Subtypes and Its Relation to Taxane Resistance

Cancers, Vol. 10, Pages 274: Genetics and Expression Profile of the Tubulin Gene Superfamily in Breast Cancer Subtypes and Its Relation to Taxane Resistance

Cancers doi: 10.3390/cancers10080274

Authors: Babak Nami Zhixiang Wang

Taxanes are a class of chemotherapeutic agents that inhibit cell division by disrupting the mitotic spindle through the stabilization of microtubules. Most breast cancer (BC) tumors show resistance against taxanes partially due to alterations in tubulin genes. In this project we investigated tubulin isoforms in BC to explore any correlation between tubulin alterations and taxane resistance. Genetic alteration and expression profiling of 28 tubulin isoforms in 6714 BC tumor samples from 4205 BC cases were analyzed. Protein-protein, drug-protein and alterations neighbor genes in tubulin pathways were examined in the tumor samples. To study correlation between promoter activity and expression of the tubulin isoforms in BC, we analyzed the ChIP-seq enrichment of active promoter histone mark H3K4me3 and mRNA expression profile of MCF-7, ZR-75-30, SKBR-3 and MDA-MB-231 cell lines. Potential correlation between tubulin alterations and taxane resistance, were investigated by studying the expression profile of taxane-sensitive and resistant BC tumors also the MDA-MB-231 cells acquired resistance to paclitaxel. All genomic data were obtained from public databases. Results showed that TUBD1 and TUBB3 were the most frequently amplified and deleted tubulin genes in the BC tumors respectively. The interaction analysis showed physical interactions of &alpha;-, &beta;- and &gamma;-tubulin isoforms with each other. The most of FDA-approved tubulin inhibitor drugs including taxanes target only &beta;-tubulins. The analysis also revealed sex tubulin-interacting neighbor proteins including ENCCT3, NEK2, PFDN2, PTP4A3, SDCCAG8 and TBCE which were altered in at least 20% of the tumors. Three of them are tubulin-specific chaperons responsible for tubulin protein folding. Expression of tubulin genes in BC cell lines were correlated with H3K4me3 enrichment on their promoter chromatin. Analyzing expression profile of BC tumors and tumor-adjacent normal breast tissues showed upregulation of TUBA1A, TUBA1C, TUBB and TUBB3 and downregulation of TUBB2A, TUBB2B, TUBB6, TUBB7P pseudogene, and TUBGCP2 in the tumor tissues compared to the normal breast tissues. Analyzing taxane-sensitive versus taxane-resistant tumors revealed that expression of TUBB3 and TUBB6 was significantly downregulated in the taxane-resistant tumors. Our results suggest that downregulation of tumor &beta;III- and &beta;V-tubulins is correlated with taxane resistance in BC. Based on our results, we conclude that aberrant protein folding of tubulins due to mutation and/or dysfunction of tubulin-specific chaperons may be potential mechanisms of taxane resistance. Thus, we propose studying the molecular pathology of tubulin mutations and folding in BC and their impacts on taxane resistance.

https://ift.tt/2MkCIG0

Investigational therapies targeting the androgen signaling axis and the androgen receptor and in prostate cancer - recent developments and future directions.

Investigational therapies targeting the androgen signaling axis and the androgen receptor and in prostate cancer - recent developments and future directions.

Expert Opin Investig Drugs. 2018 Aug 17;:

Authors: Isaacsson Velho P, Carducci MA

Abstract
INTRODUCTION: Despite the heterogeneity of prostate cancer (PCa), androgen stimulation is fundamental to its development, growth and lethality. Therefore, the blockade of androgen receptor (AR) signaling is critical to controlling the disease, even after progression with castrate levels of androgens. Areas covered: We review the current understanding of new ways to block the AR, using novel antiandrogen inhibitors, which act on different parts of the AR signaling pathway in PCa. We also review new approaches, such as the use of poly (ADP-ribose) polymerase (PARP) inhibitors, targeting both the AR and the DNA repair pathway, potentially adding synergy and improving efficacy and the combination of AR inhibitors and immunotherapy. Bipolar androgen therapy (BAT), an innovative strategy to target the AR, has shown early evidence of efficacy in PCa is also discussed in detail. We highlight some of the key ongoing studies of greatest relevance to this topic. Expert commentary: Clinical trials investigating new AR targeted therapies should be encouraged in patients with PCa. While it is unlikely that one AR inhibitor will produce long-lasting responses in a substantial proportion of patients, there is evidence that some strategies, such as the BAT could resensitize the AR to antiandrogens, alternating therapies and delaying time to progression, maximizing benefit to patients.

PMID: 30118330 [PubMed - as supplied by publisher]

https://ift.tt/2L4Qk2W

Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review of Literature.

Related Articles

Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review of Literature.

Gastroenterology Res. 2018 Aug;11(4):264-273

Authors: Baran B, Mert Ozupek N, Yerli Tetik N, Acar E, Bekcioglu O, Baskin Y

Abstract
Colorectal cancer is the third most common cancer worldwide with a high mortality rate at the advanced stages. However, colorectal cancer is not a single type of tumor; its pathogenesis depends on the anatomical location of the tumor and differs between right side and left side of the colon. Tumors in the proximal colon (right side) and distal colon (left side) exhibit different molecular characteristics and histology. In the right-sided tumors, mutations in the DNA mismatch repair pathway are commonly observed; and these tumors generally have a flat histology. In the left-sided tumors, chromosomal instability pathway-related mutations, such as KRAS, APC, PIK3CA, p53 mutations are observed and these tumors demonstrate polypoid-like morphology. Therapy responses are totally different between these tumor entities. Left-sided colorectal cancer (LCRC) patients benefit more from adjuvant chemotherapies such as 5-fluorouracil (5-FU)-based regimes, and targeted therapies such as anti- epidermal growth factor receptor (EGFR) therapy, and have a better prognosis. Right-sided colorectal cancer (RCRC) patients do not respond well to conventional chemotherapies, but demonstrate more promising results with immunotherapies because these tumors have high antigenic load. For the development of effective therapy regimes and better treatment options, it is essential to evaluate right-sided and left-sided tumors as separate entities, and design the therapy regime considering the differences between these tumors.

PMID: 30116425 [PubMed]

https://ift.tt/2BpkMoM

Expression of Pro- and Antiapoptotic Factors in Multinuclear Macrophages of BCG-Infected Mice In Vitro

Intraperitoneal infection of Mycobacterium tuberculosis from BCG vaccine to male BALB/c mice provoked the formation of multinuclear macrophages in the peritoneal transudate. In 2 and 3 months after infection, their number increased respectively by 34.4 and 66.7% in comparison with intact mice. At all postinfection terms, far greater amounts of caspase 3, p53, Bad, and TNFα were expressed by multinuclear macrophages than by the mononuclear ones. At these terms, the content of Bcl-2-expressing macrophages with different numbers of nuclei was pronouncedly high; of them, the number of multinuclear macrophages was maximum. In 3 months after infection, the number of macrophages expressing Bcl-2 significantly decreased irrespective of the number of their nuclei. At this term, the number of macrophages expressing caspase 3, and TNFα also decreased. In parallel, the number of macrophages expressing p53 and Bad somewhat increased. These data attest to potentiality ("readiness") of macrophages infected with Mycobacterium tuberculosis to apoptotic self-elimination.

https://ift.tt/2wcWMiT

Effect of Lithium Preparations on Cerebral Electrophysiological Activity in Rats

The study examined the effects of a novel neurotropic medication based on a lithium complex composed of lithium citrate, polymethylsiloxane, and aluminum oxide on electrophysiological parameters of the rat brain. In contrast to lithium carbonate (the reference drug), the novel preparation resulted in a wave-like dynamics of electrical activity in the visual cortex. Rhythmic photic stimulation of the rats treated with lithium carbonate resulted in appearance of the signs attesting to up-regulation of excitability of cerebral cortex in all examined ranges. In contrast, the complex lithium preparation diminished the delta power spectrum, which was the only affected frequency band. It is hypothesized that the complex lithium medication induces milder activation of the cerebral cortex in comparison with lithium carbonate. The novel medication composed of lithium citrate, aluminum oxide, and polymethylsiloxane, is characterized by greater efficacy and safety than the preparation based on inorganic lithium salt (lithium carbonate).

https://ift.tt/2nM2lRB

Disintegration of Bacterial Film by Electrochemically Activated Water Solution

The structure of bacterial film formed at the inner surface of the recirculation reactor tube, is studied. The surface relief of the biofilm was visualized by scanning electron microscopy. The effect of electrochemically activated water solution on the film formed from planktonic lactobacteria or E. coli was studied. Treatment with electrochemically activated water solution destroys cells and polymeric matrix of the biofilm.

https://ift.tt/2we8ERt

Correlation of Cognitive Abilities of Male Hamadryas Baboon with Age and Hierarchical Status

We studied the correlation between the rank and age of baboons (n=12) with their cognitive abilities. A positive correlation was found between performances of different tests by male. The ability to solve the tests related to bait placement depended on the age of the males and age-related hierarchical status. Four-year-old males performed these tests in 52% of cases, whereas five-year-old males, who reached a higher hierarchical status by this age solved with them in 93% of cases. In the tests for exploratory activity and the ability to learn skills, the differences between the four-year-olds and the five-year-old males are not received.

https://ift.tt/2nMY1RW

Hemodynamic Allostasis of Pregnant Women against the Background of Preeclampsia

We analyzed diurnal hemodynamic parameters (HR, systolic BP, and diastolic BP) recorded from two groups of edematous and preeclamptic pregnant women. The unidirectional character of changes in the control over the functional state of cardiovascular system was revealed except for the indices, which mark a pathological process: elevated diurnal BP in preeclampsia and diminished percentage of oscillation power in edematous patients. Uniformity of the regulatory changes in patients with and without arterial hypertension can be viewed as manifestation of allostasis developed by the cardiovascular system during pregnancy. In preeclampsia, the greater allostatic load was reflected by the changes in diurnal, daytime, and nighttime BP and in the circadian index calculated for HR, systolic BP, and diastolic BP. In edematous patients, elevation of allostatic load was indicated by the percentage of ultradian rhythms.

https://ift.tt/2wcWJ6H

Evaluation of the cardiac safety of long‐acting endectocide moxidectin in a randomized concentration‐QT study

Clinical and Translational Science, Volume 0, Issue ja, -Not available-.


https://ift.tt/2nNCwkb

Influence of liver fibrosis on prognosis after surgical resection for resectable single hepatocellular carcinoma

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2L4idrB

Intestinal epithelial cells and T cells differentially recognize and respond to Candida albicans yeast and hypha

European Journal of Immunology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2BoAgcI

General Surgery Prioritization Tool: a pilot study

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2vSm8TP

Prevalence of low anterior resection syndrome at a regional Australian centre

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2vQrfE8

Unique case of atypical type A thymoma with vertebral metastasis and high 18‐fluorodeoxyglucose avidity

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2KZVj4Q

Improvement of anaphylactoid purpura in a patient with ascending colon cancer after colectomy

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2vSYmqK

Pulmonary sequestration mimicking lung abscess in old age

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2L4i8Ej

Early outcomes of two‐stage minimally invasive oesophagectomy in an Australian institution

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2vQm5ro

Detecting tumour response and predicting resectability after neoadjuvant therapy for borderline resectable and locally advanced pancreatic cancer

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2L2kMuz

Signet cell carcinoma of the colon: a rare presentation to a rural surgical service

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2vUS1v0

Nomogram predicting survival of hepatocellular carcinoma with portal vein tumour thrombus after curative resection

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2L4ITsy

Rare adrenal ganglioneuroma encasing the inferior vena cava

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2vQ8OiI

Anatomical variations in the first extensor compartment: a cadaver study

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2L6j5fv

Intraoperative diagnosis of a duplicated cystic duct

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2vUQEwj

Laparoscopic treatment for an inguinal Richter's hernia: an unusual indication in case of acute small bowel obstruction

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2L3mc83

Acute Blood Pressure Management in Acute Ischemic Stroke and Spontaneous Cerebral Hemorrhage

Abstract

Purpose of review

We discuss the evidence and guidelines for acute blood pressure (BP) management for patients presenting with acute ischemic stroke or spontaneous cerebral hemorrhage.

Recent findings

Observational data suggest that the extremes of BP should be avoided in patients presenting with acute ischemic stroke. There is no convincing evidence that active BP reduction results in improved outcomes for ischemic stroke patients. Current guidelines recommend that BP be maintained ≤ 185/110 mmHg in patients who are candidates for intravenous tissue plasminogen activator (IV tPA) or mechanical thrombectomy and that BP be maintained ≤ 180/105 mmHg for at least 24 h in patients who have received IV tPA or have undergone mechanical thrombectomy. Acute BP goals for spontaneous cerebral hemorrhage remain unclear despite a number of randomized controlled trials.

Summary

Acute BP goals for patients with acute ischemic stroke largely depend on candidacy for, and receipt of, IV tPA and mechanical thrombectomy. As thrombectomy is now the standard of care for many patients with large vessel occlusion, we will see a heightened interest in pre- and post-thrombectomy BP management. Future trials of spontaneous cerebral hemorrhage may focus on hyperacute BP lowering (e.g., in the prehospital setting).

https://ift.tt/2MkN499